Selective spread and reduced virus release leads to canine distemper virus persistence in the nervous system

In primary dog brain cell cultures (DBCC) the attenuated canine distemper virus (CDV) is cytolytic, whereas virulent CDV is not. Thus, the question why cytolysis does or does not occur appears to be intimately associated with the mechanism of persistence. Persistence is most likely related to the way these viruses replicate. In the present study we used morphological and immunocytochemical approaches to compare several aspects of virus replication between a cytolytic and a virulent CDV strain using DBCC to study both strains. Quantitative measurements did not detect a difference in the rate of virus protein synthesis at the level of the single cell, between the two types of infection. Electron microscopical results and virus titration experiments showed marked differences in virus spread and virus release. Immunocytochemical studies showed differences in the distribution of the nucleocapsid and matrix proteins between the two infections. Budding and cytolysis are strongly limited in the virulent A75/17-CDV infection as compared to attenuated viruses. This is probably due to structural changes in the virus proteins leading to modifications of virus assembly. Thus the present study supports a mechanism of CDV persistence through a type of virus maturation and spread by which very little virus is released outside of the cell.